Canadian scientists transform human skin into blood

Sharon Kirkey, Postmedia News11.07.2010

Dr. Mickie Bhatia (photographed in his McMaster University lab in Hamilton on November 5, 2010) director the of stem cell and cancer research institute at McMaster University in Hamilton and his team of researchers have been able to create blood directly from adult skin cells.

Canadian scientists have transformed pinches of human skin into petri dishes of human blood — a major medical breakthrough that could yield new sources of blood for transfusions after cancer treatments or surgery.

The discovery, by researchers at McMaster University in Hamilton, Ont., could one day potentially allow anyone needing blood after multiple rounds of surgery or chemotherapy, or for blood disorders such as anemia, to have a backup supply of blood created from a tiny patch of their own skin — eliminating the risk of their body’s immune system rejecting blood from a donor.

Researchers predict the lab-grown blood could be ready for testing in humans within two years.

The achievement, published Sunday in the journal Nature, raises the possibility of personalizing blood production for patients for the first time.

"This is a very important discovery. I think it represents a seminal contribution" to the rapidly evolving field of stem-cell research, said Michael Rudnicki, scientific director of the Canadian Stem Cell Network and director of the Regenerative Medicine Program at the Ottawa Hospital Research Institute.

"That one can play with the fate of a cell and force it sideways into something that it doesn’t at all resemble, and then being able to use it, is tremendously exciting."

The procedure is also relatively simple. It involves taking a small piece of skin just centimetres in size, which would require only a stitch to close, extracting fibroblasts — abundant cells in the skin that make up the connective tissue and give skin its flexibility — and bathing them in growth factors in a petri dish. Next, by adding a single protein that binds to DNA and acts as an on/off switch, the researchers turned on or off some 2,000 genes and reprogrammed the skin cells to differentiate or morph into millions of blood progenitors — the cells the produce blood.

They generated multiple different blood-cell types — oxygen-ferrying red blood cells, infection-fighting white blood cells, cells that make platelets needed for healing, and macrophages, the garbage trucks of the blood system that swallow and break down foreign material.

The work was repeated several times over two years using skin from adults, as well as neonatal foreskin, demonstrating, according to background material, that it could work "for any age of person."

And while other researchers have reprogrammed fibroblasts into neurons, cardiac cells and even macrophage-like cells in mice, the McMaster team converted skin directly to blood using human skin.

The first to benefit could be patients with leukemia, whose blood undergoes genetic changes that turn it cancerous and who often need-bone marrow transplants, or those with lymphomas, such as Hodgkin’s disease.

Bone marrow contains stem cells that produce blood cells. If the bone marrow is coming from a donor, "first of all, you have to find a match, which can often be a problem, especially for smaller ethnic groups," says Dr. Christine Williams, director of research at the Canadian Cancer Society Research Institute. There’s also a risk of rejection, where the body sees the matched cells as foreign.

Using a patient’s own bone marrow gets around the rejection risk. "But if you take the patient’s own blood stem cells and put them back in after radiation, you’re often re-transplanting cells that have the same mutation as the tumour," Williams says.

The skin cells of leukemia patients "don’t have any genetic abnormalities," says Mick Bhatia, leader of the McMaster team. "So, if we could take the skin cells and generate blood, we could use that to transplant leukemic patients themselves," says Bhatia, scientific director of McMaster’s Stem Cell and Cancer Research Institute in the Michael G. DeGroote School of Medicine.

The procedure wouldn’t be limited to leukemia, Bhatia says. Heavy doses of chemotherapy for solid tumours, such as cancers of the breast, lung or prostate, not only kills cancer cells, "It also kills your blood system," Bhatia says.

Treatment often has to be stopped to give the patient’s immune system time to recover. The problem, however, is that also gives the tumour time to recover and re-grow; often the cells that re-grow from the tumour are resistant to chemotherapy.

"If you had an alternative source of blood that could be added to the chemotherapy, you could continue the chemotherapy and at higher doses, increasing the chances of killing the tumour, permanently," Bhatia says.

He says a four-by-three-centimetre patch of skin "that can be easily removed from a patient without any harm at all" — and the size surgeons now use to grow new skin for burn patients — could generate enough blood to transfuse a person. "But these are just calculations and there’s lots of work ahead to better the system we have in place now."

Bhatia says the technique could be used to freeze and store different blood types.

What makes the Canadian discovery unique is that the team made blood from human skin by skipping the middle step of changing a skin stem cell into an "induced pluripotent" stem cell — cells that act like embryonic stem cells that can turn into virtually any cell type in the body — and then turning it into a blood cell. Instead, the Canadians went straight from skin, to blood.

They also avoided the ethically sticky issuing of using cells harvested from human embryos.

"We think our process is quicker, but it also makes the right types of blood cells. It makes adult blood, because it comes from adult skin," Bhatia says. The blood from embryonic or induced pluripotent stem cells has a different type of hemoglobin, "which isn’t very useful when you transplant it into an adult."

When the team transplanted their lab-grown, skin-to-blood cells into mice that didn’t have an immune system — so that the rodents wouldn’t reject the human cells — the cells continued to form blood "for a good period,” and did not shown any sign of cancer formation, Bhatia said.

The finding — which comes nearly 50 years after blood stem cells were first identified in Canada — has the potential of "making bone marrow transplant HLA (tissue) matching and paucity of donors a thing of the past," Alain Beaudet, president of the Canadian Institutes of Health Research, which helped fund the study, said in a statement.

The Canadian Blood Services stressed that there are still no substitutes for human blood, and that donors are needed as much as ever.

"Long term, they may be able to generate red blood cells at sufficient quantity that might have some viable use in transfusion services," said senior scientist Dr. Mark Scott.

"However, at this point, there are no substitutes for donated blood, and we entirely rely upon our volunteer blood donors to provide the blood products that we need. This is not going to change in the foreseeable future," Scott said.

He said red blood cells produced in lab dishes would not only have to be safe for human use, but also produced in sufficient enough quantities "to actually meet the needs of a transfusion recipient."

Rudnicki, of the Stem Cell Network, said the work "demonstrates once again Canadian leadership in the stem-cell arena."

It comes just days after parliamentarians were warned that Canada risks losing its reputation as a world-leader in stem-cell research. Researchers last week warned the House of Common health committee that funding is drying up, and that Canada is quickly being overtaken by other jurisdictions that are spending massive amounts in stem-cell science.

California alone is investing $3 billion US over a 10-year period. According to the Canadian Institutes of Health Research, the federal government’s main research funding arm, $41.5 million was invested in stem-cell science in past fiscal year.

With files from Meagan Fitzpatrick, Postmedia News

skirkey@postmedia.com

twitter.com/sharon_kirkey

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Canadian scientists transform human skin into blood

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